ArticleOncogene2013
Stabilization of HIF-2α through redox regulation of mTORC2 activation and initiation of mRNA translation.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer.The Journal of clinical investigation · 2026Article
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- Iron Deficiency Impairs Muscle Stem Cell Proliferation and Skeletal Muscle Regeneration via HIF-2α Stabilization.Journal of cachexia, sarcopenia and muscle · 2025Article
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- Vitamin D and Hypoxia: Points of Interplay in Cancer.Cancers · 2022Review
- Article
- Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox biology · 2020Review
- Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy.Investigative ophthalmology & visual science · 2020Article
- Prognostic Value of YTHDF2 in Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2020Article
- Hypoxia‑inducible factors in hepatocellular carcinoma (Review).Oncology reports · 2020Review
- Hypoxia-inducible factor (HIF)-prolyl hydroxylase 3 (PHD3) maintains highThe Journal of biological chemistry · 2019Article
- Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies.Clinical & experimental metastasis · 2018Review
- Article
- Mitochondrial ROS control of cancer.Seminars in cancer biology · 2017Review
- NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance.Nature communications · 2017Article
- Redox control of senescence and age-related disease.Redox biology · 2017Review
- RTP801 Amplifies Nicotinamide Adenine Dinucleotide Phosphate Oxidase-4-Dependent Oxidative Stress Induced by Cigarette Smoke.American journal of respiratory cell and molecular biology · 2017Article
- mTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes.Antioxidants & redox signaling · 2016Article
- Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved.Antioxidants & redox signaling · 2016Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia inducible factor-2α (HIF-2α) has a critical role in renal tumorigenesis. HIF-2α is stabilized in von Hippel-Lindau (VHL)-deficient renal cell carcinoma through mechanisms that require ongoing mRNA translation. Mammalian target of rapamycin (mTOR) functions in two distinct complexes: Raptor-associated mTORC1 and Rictor-associated mTORC2. Rictor-associated mTORC2 complex has been linked to maintaining HIF-2α protein in the absence of VHL; however, the mechanisms remain to be elucidated. Although Raptor-associated mTORC1 is a known key upstream regulator of mRNA translation, initiation and elongation, the role of mTORC2 in regulating mRNA translation is not clear. Complex assembly of the mRNA cap protein, eukaryotic translation initiation factor 4 (eIF4)E, with activators (eIF4 gamma (eIF4G)) and inhibitors (eIF4E-binding protein 1 (4E-BP1)) are rate-limiting determinants of mRNA translation. Our laboratory has previously demonstrated that reactive oxygen species, mediated by p22(phox)-based Nox oxidases, are enhanced in VHL-deficient cells and have a role in the activation of Akt on S473, a site phosphorylated by the mTORC2 complex. In this study, we examined the role of Rictor-dependent regulation of HIF-2α through eIF4E-dependent mRNA translation and examined the effects of p22(phox)-based Nox oxidases on TORC2 regulation. We demonstrate for the first time that mTORC2 complex stability and activation is redox sensitive, and further defined a novel role for p22(phox)-based Nox oxidases in eIF4E-dependent mRNA translation through mTORC2. Furthermore, we provide the first evidence that silencing of p22(phox) reduces HIF-2α-dependent gene targeting in vitro and tumor formation in vivo. The clinical relevance of these studies is demonstrated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.